Comparison of Plasma Ionization- and Secondary Electrospray Ionization- High-resolution Mass Spectrometry for Real-time Breath Analysis

Jiafa Zeng, Alexandra Christen, Kapil Dev Singh, Urs Frey, and Pablo Sinues

Abstract: Real-time breath analysis by high-resolution mass spectrometry (HRMS) is a promising method to non-invasively retrieve relevant biochemical information. In this work, we conducted a head-to-head comparison of two ionization techniques: Secondary electrospray ionization (SESI) and plasma ionization (PI), for the analysis of exhaled breath. Two commercially available SESI and PI sources were coupled to the same HRMS device to analyze breath of two healthy individuals in a longitudinal study. We analyzed 58 breath specimens in both platforms, leading to 2,209 and 2,296 features detected by SESI-HRMS and by PI-HRMS, respectively. 60% of all the mass spectral features were detected in both platforms. However, remarkable differences were noted in terms of the signal-to-noise ratio (S/N), whereby the median (interquartile range, IQR) S/N ratio for SESI-HRMS was 115 (IQR = 408), whereas for PI-HRMS it was 5 (IQR = 5). Differences in the mass spectral profiles for the same samples make the inter-comparability of both techniques problematic. Overall, we conclude that both techniques are excellent for real-time breath analysis because of the very rich mass spectral fingerprints. However, further work is needed to fully understand the exact metabolic insights one can gather using each of these platforms.

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Trends in Direct Breath Analysis by Secondary Electrospray Ionization Mass Spectrometry for Clinical Applications

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UHPLC-MS/MS-Based Identity Confirmation of Amino Acids Involved in Response to and Side Effects from Antiseizure Medications